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Piezo2 is the major transducer of mechanical forces for touch sensation in mice

Item Type:Article
Title:Piezo2 is the major transducer of mechanical forces for touch sensation in mice
Creators Name:Ranade, S.S. and Woo, S.H. and Dubin, A.E. and Moshourab, R.A. and Wetzel, C. and Petrus, M. and Mathur, J. and Begay, V. and Coste, B. and Mainquist, J. and Wilson, A.J. and Francisco, A.G. and Reddy, K. and Qiu, Z. and Wood, J.N. and Lewin, G.R. and Patapoutian, A.
Abstract:The sense of touch provides critical information about our physical environment by transforming mechanical energy into electrical signals. It is postulated that mechanically activated cation channels initiate touch sensation, but the identity of these molecules in mammals has been elusive. Piezo2 is a rapidly adapting, mechanically activated ion channel expressed in a subset of sensory neurons of the dorsal root ganglion and in cutaneous mechanoreceptors known as Merkel-cell-neurite complexes. It has been demonstrated that Merkel cells have a role in vertebrate mechanosensation using Piezo2, particularly in shaping the type of current sent by the innervating sensory neuron; however, major aspects of touch sensation remain intact without Merkel cell activity. Here we show that mice lacking Piezo2 in both adult sensory neurons and Merkel cells exhibit a profound loss of touch sensation. We precisely localize Piezo2 to the peripheral endings of a broad range of low-threshold mechanoreceptors that innervate both hairy and glabrous skin. Most rapidly adapting, mechanically activated currents in dorsal root ganglion neuronal cultures are absent in Piezo2 conditional knockout mice, and ex vivo skin nerve preparation studies show that the mechanosensitivity of low-threshold mechanoreceptors strongly depends on Piezo2. This cellular phenotype correlates with an unprecedented behavioural phenotype: an almost complete deficit in light-touch sensation in multiple behavioural assays, without affecting other somatosensory functions. Our results highlight that a single ion channel that displays rapidly adapting, mechanically activated currents in vitro is responsible for the mechanosensitivity of most low-threshold mechanoreceptor subtypes involved in innocuous touch sensation. Notably, we find that touch and pain sensation are separable, suggesting that as-yet-unknown mechanically activated ion channel(s) must account for noxious (painful) mechanosensation.
Keywords:Cellular Mechanotransduction, Ion Channels, Mechanoreceptors, Merkel Cells, Knockout Mice, Sensory Receptor Cells, Skin, Touch, Animals, Mice
Source:Nature
ISSN:0028-0836
Publisher:Nature Publishing Group (U.K.)
Volume:516
Number:7529
Page Range:121-125
Date:4 December 2014
Official Publication:https://doi.org/10.1038/nature13980
PubMed:View item in PubMed

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